Project Summary. Noroviruses, a group of nonenveloped single-stranded RNA viruses, are the leading cause of gastroenteritis outbreaks and account for 21 million cases in the US annually. Current prevention and control options are limited with no vaccines or therapeutics available. Antibody- based norovirus diagnostic kits suffer from low sensitivity and are dependent on the antibody used. Rapid, accurate, point of care diagnostic kits are critical to detect and isolate infected personnel. We propose a novel approach by using synthetic glycans as capture molecules. In this proposal, an interdisciplinary team will develop rapid, point of care diagnostics for the sensitive detection of norovirus. In Specific Aim 1, we will use a modular synthetic strategy to generate synthetic analogs of histo-blood group antigens and Lewis antigens, attachment factors for norovirus. In Specific Aim 2, we will develop and evaluate glycan based diagnostic platforms using panels of norovirus strains In Specific Aim 3, candidate diagnostic platforms will be compared side-by-side evaluated using clinical samples from both outbreaks and sporadic cases of gastrointestinal illness. Accomplishing the specific aims in this proposal is expected to yield rapid, robust, point of care, user friendly diagnostics for the precise and sensitive detection of all human norovirus strains.